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首页> 外文期刊>Molecular Systems Biology >GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome
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GINS motion reveals replication fork progression is remarkably uniform throughout the yeast genome

机译:GINS运动显示复制叉在整个酵母基因组中的进展非常均匀

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摘要

Previous studies have led to a picture wherein the replication of DNA progresses at variable rates over different parts of the budding yeast genome. These prior experiments, focused on production of nascent DNA, have been interpreted to imply that the dynamics of replication fork progression are strongly affected by local chromatin structure/architecture, and by interaction with machineries controlling transcription, repair and epigenetic maintenance. Here, we adopted a complementary approach for assaying replication dynamics using whole genome time?¢????resolved chromatin immunoprecipitation combined with microarray analysis of the GINS complex, an integral member of the replication fork. Surprisingly, our data show that this complex progresses at highly uniform rates regardless of genomic location, revealing that replication fork dynamics in yeast is simpler and more uniform than previously envisaged. In addition, we show how the synergistic use of experiment and modeling leads to novel biological insights. In particular, a parsimonious model allowed us to accurately simulate fork movement throughout the genome and also revealed a subtle phenomenon, which we interpret as arising from low?¢????frequency fork arrest.
机译:先前的研究已经得出了这样的图景,其中DNA的复制在发芽酵母基因组的不同部分上以可变速率进行。这些先前的实验侧重于新生DNA的产生,已被解释为暗示复制叉进程的动力学受到局部染色质结构/体系结构以及与控制转录,修复和表观遗传维持的机器的相互作用的强烈影响。在这里,我们采用了一种补充方法,利用全基因组时间分辨的染色质免疫沉淀结合GINS复合物的微阵列分析(复制叉的组成部分)来测定复制动力学。出乎意料的是,我们的数据表明,无论基因组位置如何,这种复合物都以高度均匀的速率进行,这表明酵母中的复制叉动力学比以前设想的更简单,更均匀。此外,我们展示了实验和建模的协同使用如何带来新颖的生物学见解。特别是,一个简化的模型使我们能够精确地模拟叉子在整个基因组中的运动,并且还揭示了一个细微的现象,我们将其解释为由低频率的叉子停滞引起。

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